Bronchoconstriction present in several respiratory disorders, such as bronchial asthma, early airway disease, or bronchoconstriction as a result of environmental injury may be a result of airway hyperreactivity. The pathophysiological mechanism of this airway hyperreactivity is unknown. The airway smooth muscle is directly involved in this bronchoconstriction and plays a key part in the airway hyperreactive response. This research project will define the cause of airway hyperreactivity on the cellular level and will define fundamental properties of airway smooth muxcle. This includes analysis of physiological, pharmacological, electrophysiological and biochemical properties of airway smooth muscle isolated from both normal and chronically sensitized animals. Particularly important will be to investigate the mechanisms which regulate smooth muscle relaxation. Recently described system, i.e., nonadrenergic, noncholinergic nervous system (purinergic nervous system) is a system primarily responsible for relaxation of airway smooth muscle. This research project will study why this system is altered in airway smooth muscle of sensitized animals. Since the applicant's laboratory has recently demonstrated the alteration of physiological and electrophysiological properties of airway smooth muscle cells isolated from sensitized animals, an attempt will be made to define the exact cause of these changed membrane characteristics. This approach may lead toward rationalization of therapy of airway hyperreactivity and bronchoconstriction, such as present in bronchial asthma, which in most instances at present is empirical.